SEARCH:   Advanced

Blood, 1 September 2006, Vol. 108, No. 5, pp. 1716-1723. Prepublished online as a Blood First Edition Paper on May 2, 2006; DOI 10.1182/blood-2006-04-016113. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-04-016113v1 108/5/1716    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by McCallum, L. Articles by Irvine, A. E. Search for Related Content PubMed PubMed Citation Articles by McCallum, L. Articles by Irvine, A. E. Related Collections Cell Cycle Oncogenes and Tumor Suppressors Signal Transduction Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA A novel mechanism for BCR-ABL action: stimulated secretion of CCN3 is involved in growth and differentiation regulation Lynn McCallum, Susan Price, Nathalie Planque, Bernard Perbal, Andrew Pierce, Anthony D. Whetton, and Alexandra E. Irvine From the Department of Haematology, Centre for Cancer Research and Cell Biology, Queen's University Belfast, United Kingdom; Laboratoire d'Oncologie Virale et Moleculaire, UFR de Biochimie, Universite Paris7-D-Diderot, Paris, France; and the Faculty of Medical and Human Sciences, University of Manchester, Christie Hospital, Manchester, United Kingdom. Chronic myeloid leukemia (CML) is characterized by the presence of the constitutively active BCR-ABL protein tyrosine kinase. Using a multipotent hemopoietic cell line, FDCP-Mix, expressing BCR-ABL tyrosine kinase, we investigated the initial effects of this kinase in primitive hematopoietic stem cells. We identified down-regulation of a novel gene, CCN3, as a direct consequence of BCR-ABL kinase activity. CCN3 has been reported to function as a tumor suppressor gene in solid tumors. Northern and Western blotting plus immunocytochemical analysis confirmed CCN3 expression is decreased and is tyrosine-phosphorylated in BCR-ABL kinase active FDCP-Mix cells. Decreased cellular CCN3 correlated with increased CCN3 secretion in BCR-ABL kinase active cells. In vitro treatment of human CML cell lines with imatinib or siRNA directed against BCR-ABL significantly reduced BCR-ABL while increasing CCN3 expression. Cells from patients responding to imatinib showed a similar decrease in BCR-ABL and increase in CCN3. CML CD34+ cells treated with imatinib in vitro demonstrated increased CCN3 protein. Transfecting CCN3 into BCR-ABL+ cells inhibited proliferation and decreased clonogenic potential. CCN3 plays an important role in internal and external cell-signaling pathways. Thus, BCR-ABL can regulate protein levels by governing secretion, a novel mechanism for this tyrosine kinase. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. Vallacchi, M. Daniotti, F. Ratti, D. Di Stasi, P. Deho, A. De Filippo, G. Tragni, A. Balsari, A. Carbone, L. Rivoltini, et al. CCN3/Nephroblastoma Overexpressed Matricellular Protein Regulates Integrin Expression, Adhesion, and Dissemination in Melanoma Cancer Res., February 1, 2008; 68(3): 715 - 723. [Abstract] [Full Text] [PDF] M. Doghman, M. Arhatte, H. Thibout, G. Rodrigues, J. De Moura, S. Grosso, A. N. West, M. Laurent, J.-C. Mas, A. Bongain, et al. Nephroblastoma Overexpressed/Cysteine-Rich Protein 61/Connective Tissue Growth Factor/Nephroblastoma Overexpressed Gene-3 (NOV/CCN3), a Selective Adrenocortical Cell Proapoptotic Factor, Is Down-Regulated in Childhood Adrenocortical Tumors J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3253 - 3260. [Abstract] [Full Text] [PDF]

	Blood Online is supported in part by Genentech BioOncology and Biogen Idec
	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020